基于SIRT3/Foxo3抑制线粒体氧化应激的补肺益肾组分方防治PM2.5加重COPD机制

慢性阻塞性肺疾病（COPD）患病率高、死亡率高，PM2.5暴露可显著加剧其进程，尚无有效防治措施。SIRT3/Foxo3介导的线粒体氧化应激是PM2.5诱发COPD加重的重要因素。补肺益肾方治疗COPD疗效确切，补肺益肾组分方是基于其组分优化配比配伍获得的中药组分方，可改善COPD大鼠肺功能，抑制氧化应激，但对PM2.5诱发COPD加重的防治作用和机制尚不清楚。故本项目拟以前期建立的PM2.5诱发COPD加重模型大鼠和PM2.5/香烟烟雾诱导的肺上皮细胞（Beas-2B）为对象，采用肺功能、病理学、Western blot、RNAi、免疫荧光、免疫共沉淀和蛋白质谱等技术，观察补肺益肾组分方的疗效，并阐明其通过SIRT3/Foxo3抑制线粒体氧化应激防治PM2.5诱发COPD加重的机制，为寻找中医药作用新靶点提供研究基础，为临床防治PM2.5致肺损伤、诱发COPD加重的应用提供科学依据。

Chronic obstructive pulmonary disease (COPD) is a disease with high prevalence and mortality. The exposures of particulate matter with aerodynamic diameters less than 2.5 microns (PM2.5) can significantly aggravate the progression of COPD. But therapies for this condition have yet to be explored. Mitochondrial oxidative stress has been indicated to play a critical role in COPD aggravation caused by PM2.5 exposure, which can be inhibited by activating SIRT3/Foxo3 signaling to enhance antioxidative enzyme. Bufei Yishen Formula (BYF) has been confirmed efficacious in preventing COPD. Effective-component compatibility of BYF (ECC-BYF), a combination of 5 bioactive molecules of BYF, is derived from BYF. Its beneficial effect on COPD model rats has been previously demonstrated, by enhancing lung function and attenuating oxidative stress. However, it has not yet any studies characterizing the effect and mechanisms of ECC-BYF on COPD aggravation caused by PM2.5 exposure. In the current study, we focused on evaluating the effect of ECC-BYF on COPD aggravation caused by PM2.5 exposure via inhibiting mitochondrial oxidative stress via SIRT3/Foxo3 signaling by using RNA interference，Western blotting, Immunofluorescence (IF), Co-immunoprecipitation (Co-IP) and protein spectrum technologies, in PM2.5-aggravated COPD rats and PM2.5/cigarette smoke-exposed bronchial epithelial cells (Beas-2B). This study will provide a scientific basis for searching new effective target of Chinese medicine, and a research foundation for clinical application of lung injury and COPD aggravation caused by PM2.5.